Differential effects of EPA and DHA on DSS-induced colitis in mice and possible mechanisms involved. Issue 4 (1st February 2021)

• Record Type: Journal Article
• Authors: Zhang, Zhuangwei; Xue, Zhe; Yang, Haitao; Zhao, Feng; Liu, Chundi; Chen, Jiahui; Lu, Songtao; Zou, Zuquan; Zhou, Yuping; Zhang, Xiaohong
• Is Part Of: Food & function. Volume 12:Issue 4(2021)
• Page Start: 1803
• Page End: 1817
• Publication Date: 2021-02-01
• Subjects: Food -- Analysis -- Periodicals; Food -- Composition -- Periodicals; Nutrition -- Periodicals; 664.07
• DOI: 10.1039/d0fo02308f
• Languages: English
• ISSNs: 2042-6496

Abstract

Abstract : EPA, superior to DHA, significantly attenuated DSS-induced colitis involved in promoting the expression of tight junction proteins, suppressing inflammatory signaling pathways and triggering intestinal epithelial cell proliferation. Abstract : Background : The anti-inflammatory effect of n-3 PUFAs has been widely documented. Emerging evidence suggests that the main component of n-3 PUFAs, eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), may have differential effects in ulcerative colitis (UC). It was aimed to clarify their differential effects in UC. Methods : Eight-week-old male C57BL/6J mice were randomly divided into 7 groups, namely control, UC model, salicylazosulfapyridine (SASP), low-dose DHA, high-dose DHA, low-dose EPA, and high-dose EPA. DHA, EPA and SASP treatment groups were orally treated accordingly for 9 weeks. During the 5 th to 9 th week the control group was given distilled water, while other groups were given distilled water with 2% dextran sodium sulfate (DSS) to induce UC. Body weight loss, diarrhea, and stool bleeding were recorded to calculate the disease activity index (DAI). The level of tight junction proteins Claudin-1 and Occludin, and cytokines including TNF-α, IL-6, and IL-1β as well as inflammatory cell markers such as MPO, F4/80, and MCP-1 in the intestinal epithelium were measured using western blotting. Activation of IL-6/STAT3 and NLRP3/IL-1β inflammatory pathways was also assessed. Levels of proliferation-related proteins of the Wnt/β-catenin pathway with c-myc, Cyclin-D1, and PCNA were detected. Results : EPA, superior to DHA, significantly attenuated DSS-induced colitis evidenced by reduced DAI scores, cytokine production and inflammatory cell infiltration. Mechanically, EPA triggered a marked up-regulation of Claudin-1 and Occludin with down-regulation of their up-stream Akt and ERK. EPA also inhibited NLRP3/IL-1β and IL-6/STAT3 inflammatory pathways and up-regulated the Wnt/β-catenin pathway. Conclusions : EPA is more suitable to be used for the treatment of UC than DHA.